Isolation, Characterization and Structure of α-Lipoic Acid¹

Abstract

Procedures are described for the isolation of crystalline a-lipoic acid from acid-hydrolyzed liver residue. This isolation represents a 300,000to 600,000-fold concentration, with a 2.5% over-all recovery of activity in the form of crystalline alipoic acid. Data are presented which indicate that a-lipoic acid is the cyclic disulfide derived from 4,s-, 5,8or 6,s-dimercapto-n-caprylic acid.Previous studies have demonstrated that a variety of biological preparations contain a substance or substances which can replace acetate in its growthpromoting function for some lactic acid bacteria and are required for the oxidative decarboxylation of p y r u~a t e .~-~ The terms "acetate-replacing factor" and "pyruvate oxidation factor" were used to denote this biological activity, which has been shown to be exhibited by a group of chemically related catalytic agenk5t6 Biological activity corresponding to that possessed by these factors has been shown to be exhibited by concentrates of ( ' p r~t o g e n , "~ an essential growth factor for Tetrah y m e n a geleii.'These factors are released from materials of natural origin by the action of enzymes or by acid or base hydrolysis. Acid hydrolysis results in maximum release of activity in the form of only two of the active principles, which are acidic in na-(1) The isolation of crystalline a-lipoic acid was effected a t the University of Texas (LJR) and in the Lilly Resexrch Laboratories (GHFS) using a combination of procedures developed by the three cooperating groups and predominantly an assay procedure developed by one of the authors (ICG). Characterization and structural determination were carried out mainly by the other authors in the Lilly Research Laboratories.(2) B. M . Guirard, E. E. Snell and R .

Capillary zone electrophoresis study of cyclodextrin – lipoic acid host‐guest interaction

“…Since the pK a of the carboxyl group of lipoic acid is 4.8 [10] it can be assumed that it is present exclusively as charged lipoate anion under the analysis conditions. A calibration curve for lipoate anion (Fig.…”

The Chemistry and Function of Lipoic Acid

“…Calvin and co-workers noted that DL-a-lipoic acid exhibited an absorption maximum in the ultraviolet at 330 mp (c = 150), a fact which had been overlooked previously (87) due to the relatively weak absorption of a-lipoic acid in this region. This characteristic absorption was shown to be a property of the 1,2-dithiolane moiety of a-lipoic acid.…”

Enzymic Mechanisms in the Citric Acid Cycle

“…Lipoic acid is present in a variety of tissues including animal and plant tissues, yeast, and bacterial cells. It has been isolated in crystalline form from acid-hydrolyzed liver residue (200,203,205) through steps including distribution between organic solvents (benzene, chloroform, ether) and aqueous phases at various pH values, chromatography of the methyl and ethyl esters on alumina and florisil, and mild alkaline hydrolysis. Its empirical formula is C&,OzSz.…”